Organ transplantation is the procedure of replacing diseased organs or parts of organs with healthy organs of another person when diseased organs lose their functions and drugs no longer help to treat the disease. However, many attempts have been made to address the problem of the lack of donors for transplantable organs. An example thereof includes stem cell xenotransplants, which is a therapeutic method of replacing damaged cells with stem cells that are differentiated and proliferated as much as needed. However, it has a limitation in that the stem cells cannot be developed into an organ consisting of different types of cells. Therefore, xenotransplantation may be considered for use in direct replacement of organs when needed.
One of the promising alternatives for human organs is xenotransplantation using animals capable of providing a sufficient quantity of donor organs, and attempts have been made to use many animals such as monkeys and pigs to supply organs for xenotransplantation. Among these, pigs have numerous similarities with humans in terms of anatomy and physiology, and their organs are similar in size than those of humans. In addition, pigs are easy to breed, and they have a short gestation period (112 days) and large litters (6 to 12 piglets). Owing to these advantages, the use of pigs' organs has been actively studied.
An immune rejection response is a serious problem for xenotransplantation using pigs, etc. Accordingly, the present inventors have succeeded in introducing a gene coding for human HO-1 and a gene coding for TNFR1-Fc fusion protein into pig cells, thereby producing a transgenic pig in which an immune rejection response is suppressed and cells are protected from oxidative stress, and in which an inflammatory response is suppressed (Korean Patent Publication No. 10-2011-0079485). However, the transgenic pig xenograft was not able to withstand hyper-acute rejection (HAR).